The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Ferroptosis is a kind of programmed cell death, involves multi-molecular and multi-signaling pathways, and the core processes is iron overload and lipid peroxidation. It affects cancer, neurological disease, cardiovascular disease, digestive system disease, and many other diseases. While, ischemia-reperfusion injury is an extremely complex pathological process, including ischemia-reperfusion injury of the heart, brain, liver and kidney, etc., which often occurs in shock, organ surgery and organ transplantation, seriously affecting human health, and there is no effective radical treatment. However, ferroptosis is closely related to ischemia-reperfusion injury so that it is possible to find the prevention and treatment measures of ischemia-reperfusion injury by exploring the internal relationship between them. Therefore, the author tries to summarize the signaling pathways of ferroptosis, and explores the relationship between ferroptosis and ischemia-reperfusion injury of heart, brain, liver and kidney by moderating the ferroptosis targets properly to find the effective ways to treat cancer, improve inflammation and relieve other diseases.

AIM:To investigate the effects of the γ-aminobutyric acid(GABAergic)neural pathway from the anterior cingulate cortex(ACC)to the nucleus accumbens(NAc)on the regulation of irritable bowel syndrome(IBS)and its underlying mechanisms in mice.METHODS:(1)A C57BL/6J mice model of IBS was established by using chronic acute combing stress(CACS).The mice were divided into a normal group and an IBS group(n=8).The presence of IBS-like symptoms was determined through behavioural tests,an intestinal motility test and abdominal withdrawal reflex scores.(2)Fluorescence gold(FG)retrograde tracing and immunohistochemistry were used to investigate the ACC-NAc GABAergic neural pathway and to examine the activation of GABA in the ACC in IBS mice(n=8).(3)A total of 1.5 μL of normal saline(NS),GABAA receptor antagonist bicuculline(BIC)or agonist isoguvacine hydrochloride(Isog)was ad-ministered via a preburied catheter into the NAc of mice in IBS and normal groups.The mice were randomly divided into three groups(n=8):NS group,BIC group and Isog group.IBS-like symptoms were assessed.(4)The mice were prein-jected with AAV2/9-mDlx-iCre-WPRE-pA in the ACC and AAV2/2Retro Plus-hSyn-DIO-hM3D(Gq)-eGFP-WPRE-pA in the NAc and subsequently divided into four groups(n=8):NS(intraperitoneal injection)+NS(NAc microinjection)group,NS+BIC group,clozapine N-oxide(CNO)+NS group and CNO+BIC group.The mice who received AAV2/2Retro-hSyn-DIO-hM4D(Gi)-EGFP-WPRE-pA in the NAc were randomly divided into three groups(n=8):NS+NS group,NS+BIC group and CNO+NS group.Enzyme-linked immunosorbent assay(ELISA)was employed to estimate the expression levels of histamine and 5-hydroxytryptamine(5-HT)in colon tissue,and the effects of GABAergic neural pathways from ACC to NAc on IBS were studied.RESULTS:CACS induced IBS-like symptoms in mice.The results of FG retrograde tracing combined with fluorescence immunohistochemistry showed that GABA neurons of ACC could project to NAc.The injection of BIC in the NAc was found to significantly reduce anxiety-like behaviours,diarrheal symptoms and visceral hy-persensitivity in the IBS mice(P<0.05).Chemogenetic inhibition of the ACC-NAc GABAergic neurons ameliorated IBS-like symptoms in mice(P<0.05).CONCLUSION:The GABAergic pathway of ACC-NAc might be involved in the regu-lation of IBS in mice,which may be related to the release of histamine and 5-HT in colon tissue.

Objective: To evaluate the clinical characteristics and outcomes of very high risk patients with primary immunoglobulin light-chain amyloidosis (pAL) at a single center in China. Method: Clinical data, treatment and outcome of 205 pAL patients in Peking Union Medical College Hospital from January 2009 to February 2016 were retrospectively analyzed. A 'very high risk’ group includes patients with Mayo 2004 stage Ⅲb and Mayo 2012 stage 4. Results: Of 205 patients, 34 (16.6%) were defined as very high risk pAL patients. The median age at diagnosis was 57 (20-84) years, and 22 patients (64.7%) were male. All 34 patients were diagnosed with cardiac involvement, multi-organ involvement was observed in 15 patients (44.1%) , and 27 (81.8%) had New York Heart Association Class Ⅲ or Ⅳ. Median values of serum cTnI, NT-proBNP, and free light chains difference were 0.25 μg/L, 11 733 ng/L, and 403 mg/L, respectively. Eight (24.2%) had more than 10% plasma cell on the bone marrow aspirate. Sixteen (47.1%) patients received bortezomib based chemotherapy and overall hematologic response rate was 58.3%. Median overall survival (OS) was 4 months. The estimated OS at 3, 6, 12, and 24 months was 51.3%, 44.0%, 35.2%, and 29.6%, respectively. Fourteen (41.2%) patients died within 3 months after the diagnosis. The estimated 1-year survival rate for the patients who got hematologic response, without hematologic response, and palliative treatment was 90.9%, 11.1%, and 0, respectively (P<0.001) . Conclusion Patients with very high risk pAL had very poor prognosis and the early death rate remained high. Those patients who obtained hematologic remission would have significantly better outcomes.

OBJECTIVETo evaluate the usage of Mayo staging system in Chinese patients with primary light chain (LC) amyloidosis.

METHODClinical data, treatment and outcome of 162 primary LC amyloidosis patients with Mayo Clinic staging in Peking Union Medical College Hospital from January 2009 to June 2015 were retrospectively analyzed.

RESULTSThe median age of 162 patients with Mayo Clinic 2004 stage was 57 (20-81) y, of them 62.3% were male. The number of patients with stage I to III were 44 (27.2%), 69 (42.6%), and 49 (30.2%), respectively. The median overall survival was not reached, 23 months and 12 months in patients with Mayo Clinic 2004 stage I, II, and III, respectively (P<0.001). Among 128 patients with Mayo Clinic 2012 stage, 48 patients (37.5%), 32 patients (25.0%), 32 patients (25.0%) and 16 patients (12.5%) were staged as Mayo Clinic 2012 stage 1 to 4, and the median OS was not reached, not reached, 13 months and 3 months, respectively (P<0.001).

CONCLUSIONMayo Clinic staging systems had important prognostic value in patients with primary LC amyloidosis.

Adult ; Aged ; Aged, 80 and over ; Amyloidosis ; diagnosis ; Female ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Young Adult

Objective To study the differential expression of serum proteins in concanavalin A(ConA) induced liver injury mouse model and analyze the relationship between disease progression and special proteins. Methods Twenty-five male mice were randomly divided into five groups, i.e. blank control group, phosphate-buffered saline (PBS) control group, liver injury groups developed 1, 3 and 6 h after ConA injection. The sera from all five groups were removed off the albumin by ProteoExtract~(TM)albumin removal kit. Then two dimensional electrophoresis ( 2DE) and mass spectrometry analysis were utilized to identify differences in protein expressions. Results Two specific proteins were detected in the liver injury group developed 6 h after ConA injection, which were identified as serum amyloid A-2 protein precursor and serum amyloid A-l protein precursor by mass spectrometry. Conclusions Serum amyloid A-2 protein precursor and serum amyloid A-l protein precursor are found at 6 h of ConA injection in ConA induced liver injury mouse model, which may be related to disease progression.